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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin slitin Jakob Neef shashank s.chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Applicability of unique scarf joint configuration in friction stir welding of AA6061-T6:Analysis of torque,force,microstructure and mechanical properties

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Defence Technology（防务技术） 2022年第4期18卷 567-582页

作者： Durjyodhan sethi Uttam Acharya shashank shekhar Barnik saha Roy Department of Mechanical Engineering National Institute of Technology AgartalaBarjalaJiraniaWest TripuraPin-799046India Department of Materials science and Engineering Indian Institute of Technology KanpurKanpur208016India

The present research introduces a unique concept of scarf joint technique in friction stir welding(FsW) of aluminum alloy AA 6061-T6 plates and an investigation on weld quality.A new joint configuration with two distinct scarf angles(75°and 60°) was considered in this *** various aspects of welding were compared with contemporary simple square butt(ssB) joint *** was carried out at a constant tool rotation speed(TRs),tool traverse speed(TTs) and tool tilt angle of 1100 rpm,2 mm/s and2°,*** results are analyzed in terms of force and torque distribution,microstructure,macrostructure,and mechanical property perspective for different joint *** study reveals the minimum amount of force and torque at 60°scarf angle joint configuration compared to that of square butt joint *** study shows that all the joints were defect-free,and a prominent onion ring was present in the lower portion of the weld nugget(WN).Fine equiaxed grains with a minimum average grain size diameter of 6.82 μm were obtained in the WN of scarf joint configuration(sJC).The maximum ultimate tensile strength(UTs) and maximum average NZ hardness of 267 MPa and83.82 HV0.1were obtained in sJC3 at a scarf angle of 60°.It has been observed from the investigation that the joint efficiency increases from 72.5%(ssB) to 86%(sJC3) at a 60° scarf *** unique characteristic may lay an impetus on probable joint strength enhancement technique without increasing the production cost.

关键词： Friction stir welding Joint configuration Al alloys Force and torque Microstructure Mechanical property

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A Micro-structure Dependent Buckling Analysis of Partially-Cracked Generally Orthotropic Plate under Thermal Domain

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Advances in Applied Mathematics and Mechanics 2023年第1期15卷 244-266页

作者： Ankur Gupta shashank soni N.K.Jain Department of Mechanical Engineering National Institute of TechnologyRaipurChhattisgarh 492010India

In this work,a non-classical analytical approach for buckling analysis of partially cracked generally orthotropic plate is proposed under the thermal *** derivation for the governing equation is based on the non-classical approach using Kirchhoff’s thin plate theory and the modified couple stress *** effect of fibre orientation on critical buckling temperature is incorporated by considering the coefficients of mutual *** spring model is applied with some modifications to formulate all the crack terms while the thermal effects are introduced in form of thermal in-plane moments and *** final governing equation is solved using Galerkin’s method and the relation for critical buckling temperature as affected by fibre orientation is *** variation of critical buckling temperature as affected by fibre orientation for different values of crack length,crack location and length scale parameter is ***,the effect of fibre orientation on fundamental frequency under the thermal domain is analysed.

关键词： Orthotropic plate fibre orientation crack microstructure thermal domain

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Additive friction stir deposition of AZ31B magnesium alloy

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Journal of Magnesium and Alloys 2022年第9期10卷 2404-2420页

作者： sameehan s.Joshi shreyash M.Patil sangram Mazumder shashank sharma Daniel A.Riley shelden Dowden Rajarshi Banerjee Narendra B.Dahotre Department of Materials science and Engineering University of North Texas3940 N Elm StDentonTX 76207USA Center for Agile and Adaptive Additive Manufacturing University of North Texas3940 N Elm StDentonTX 76207USA

The current work explored additive friction stir deposition of AZ31B magnesium alloy with the aid of MELD?***31B magnesium bar stock was fed through a hollow friction stir tool rotating at constant velocity of 400 rpm and translating at linear velocity varied from 4.2 to 6.3 mm/s.A single wall consisting of five layers with each layer of 140×40×1 mm^(3)dimensions was deposited under each processing ***,phase,and crystallographic texture evolutions as a function of additive friction stir deposition parameters were studied with the aid of scanning electron microscopy including electron back scatter diffraction and X-ray *** feed material and additively produced samples consisted of theα-Mg *** additively produced samples exhibited a refined grain structure compared to the feed *** feed material appeared to have a weak basal texture,while the additively produced samples experienced a strengthening of this basal *** additively produced samples showed a marginally higher hardness compared to the feed *** current work provided a pathway for solid state additive manufacturing of Mg suitable for structural applications such as automotive components and consumable biomedical implants.

关键词： Additive friction stir deposition Magnesium alloys Additive manufacturing Thermomechanical processing Materials processing solid state additive manufacturing

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Role of prostate cancer stem-like cells in the development of antiandrogen resistance

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Cancer Drug Resistance 2022年第2期5卷 459-471页

作者： Prem Prakash Kushwaha shiv Verma shashank Kumar sanjay Gupta Department of Urology Case Western Reserve UniversityClevelandOH 44106USA. The Urology Institute University Hospitals Cleveland Medical CenterClevelandOH 44106USA. Molecular signaling and Drug Discovery Laboratory Department of BiochemistryCentral University of PunjabBathinda 151401India. Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA. Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA. Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA. Divison of General Medical sciences Case Comprehensive Cancer CenterClevelandOH 44106USA.

Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate *** with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer(CRPC).Present research establishes that prostate cancer stem-like cells(CsCs)play a central role in the development of treatment resistance followed by disease *** CsCs are capable of self-renewal,differentiation,and regenerating tumor *** stemness properties in prostate CsCs arise due to various factors such as androgen receptor mutation and variants,epigenetic and genetic modifications leading to alteration in the tumor microenvironment,changes in ATP-binding cassette(ABC)transporters,and adaptations in molecular signaling *** reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1(ALDH1A1),Prominin 1(PROM1/CD133),Indian blood group(CD44),sRY-Box Transcription Factor 2(sox2),POU Class 5 Homeobox 1(POU5F1/Oct4),Nanog and ABC *** markers indicate enhanced self-renewal and stemness stimulating CRPC evolution,metastatic colonization,and resistance to *** this review,we discuss the role of ADT in prostate CsCs differentiation and acquisition of CRPC,their isolation,identification and characterization,as well as the factors and pathways contributing to CsCs expansion and therapeutic opportunities.

关键词： Prostate cancer second-generation antiandrogens cancer stem cells castration resistance prostate cancer androgen deprivation therapy

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A systematic Review and Meta-Analysis of Randomized Control Trials to Check Role of Non-steroidal Anti-inflammatory Drugs as Protective Factor in Alzheimer Disease subjects

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Advances in Alzheimer's Disease 2023年第1期12卷 1-16页

作者： Akash Asthana shashank Tripathi Rachna Agarwal Department of statistics University of Lucknow Lucknow India Department of Neurochemistry Institute of Human Behavior and Allied Sciences New Delhi India

Background: Alzheimer’s disease is the major neurodegenerative disease, affecting more than two third cases of dementia in the world. NsAIDs are widely used anti-inflammatory analgesic agents representing 7.7% of worldwide prescriptions of which 90% are in patients over 65 years old. Based on mixed findings observed by different RCTs, a systematic review and meta-analysis were conducted to develop a better understanding of the protective role of Non-steroidal anti-inflammatory drugs (NsAIDs) in AD. Methods: Database search was Pubmed, Webscience, and Embase. RCTs investigating the effect of NsAIDs on AD or test scores assessing cognitive function in people without AD at baseline were included. Three indicators were MMsE score, ADAs-cog score, and CDR-sob. 10 studies were included in the present Meta-analysis. Results: For the ADAs-cog score, the pooled effect size was -0.31 with 95% CI -0.06 to 0.02, which was statistically significant (p = 0.03). MMsE score difference, the pooled effect size was -0.06 with 95% CI -0.22 to 0.10, which was statistically insignificant (p-value = 0.47). For the MMsE average score, the pooled effect size was -0.002 with 95% CI -0.03 to 0.07, which was statistically insignificant (p-value = 0.87). For the CDR-sob score difference, the pooled effect size calculated using the random effect model was -0.06 with 95% CI -0.39 to 0.05 which was statistically insignificant (p = 0.14). For CDR-sob average score, the pooled effect size calculated using the random effect model was 0.21 with 95% CI -0.09 to 0.51, which was statistically insignificant (p-value = 0.17). Conclusion: Present Meta-analysis shows that NsAIDs in general are not effective in the treatment of AD. They also have no protective effect against the development of AD on their sustained use.

关键词： NsAIDs Alzheimer’s Disease Meta-Analysis Hazard Ratio

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Non-steroidal Anti-Inflammatory Drugs as Protective Factor in Alzheimer’s Diseases: A systematic Review and Meta-Analysis Protocol

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Advances in Alzheimer's Disease 2023年第2期12卷 17-28页

作者： Akash Asthana Rachna Agarwal shashank Tripathi Department of statistics University of Lucknow Lucknow India Department of Neurochemistry Institute of Human Behavior and Allied Sciences New Delhi India

Introduction: NsAIDs inhibit COX-2, which is responsible for regulating neurons leading to neurodegeneration in Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative disease affecting the geriatric population, as it affects more than two third cases of dementia in the sphere. Results obtained from experimental and observational studies were unclear regarding the protective role of NsAIDs in AD, therefore this justifies the need for meta-analysis. Methods: Database search was PubMed, Web of science, and Embase. Experimental studies and Observational studies investigating the effect of NsAIDs on AD. For experimental studies indicators used were MMsE score, ADAs-cog score, CDR-sob score, NPI score, and Hazard ratio. similarly for Observational studies, Odds Ratio and Relative Risk are used. Results: As this is the study protocol, therefore it is not possible to write the results of the study in the study protocol. There is a total of 06 (MMsE, ADAs-cog, CDR-sob, HR, RR, and OR) indicators used in the study, so 06 results will be obtained showing the pooled effect size which will indicate the use of NsAIDs as a protective factor for Alzheimer’s disease. Discussion: The present systematic review will improve the understanding of the relative efficacies of NsAIDs in AD and possibly guide clinical practices by providing the current best evidence on the efficacy of various regimens of NsAIDs in the management of AD subjects. Conclusion: Conclusion can be drawn only after the final meta-analysis using three study design (RCT, Cohort and Case-control study designs) and six indicators.

关键词： Alzheimer’s Disease NsAIDs Meta-Analysis RCT OR RR

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China's treatment regimen for fulminant myocarditis is bringing wonderful achievement to the world

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science China(Life sciences) 2019年第2期62卷 282-284页

作者： Jing Zhang Weijian Hang Rutai Hui Qiong Zhao shashank s.Desai Cardiovascalar Intensive Care Unit Fuwai Huazhong Cardiovascular Hospital Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science & Technology Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Advanced Heart Failure/Transplant Program Inova Heart and Vascular Institute Inova Fairfax Hospital

Fulminant myocarditis is characterized by acute and severe inflammation with injury of myocardium globally. It has a fulminant course and high in-hospital mortality rate of up to50%-70%. It onsets rapidly after viral ... 详细信息

关键词： China’s treatment regimen for fulminant myocarditis is bringing wonderful achievement to the world

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Decay rates of charmonia within a quark-antiquark confining potential

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Chinese Physics C 2016年第5期40卷 14-23页

作者： smruti Patel P.C.Vinodkumar shashank Bhatnagar Department of Physics Sardar Patel University Department of Physics Addis Ababa University

In this work, we investigate the spectroscopy and decay rates of charmonia within the framework of the non-relativistic schrsdinger equation by employing an approximate inter quark-antiquark potential. The spin hyperfine, spin-orbit and tensor components of the one gluon exchange interaction are employed to compute the spectroscopy of the excited s states and a few low-lying P and D waves. The resultant wave functions at zero inter- quark separation as well as some finite separations are employed to predict the di-gamma, di-leptonic and di-gluon decay rates of charmonia states using the conventional Van Royen-Weisskopf formula. The di-gamma and di-leptonic decay widths are also computed by incorporating the relativistic corrections of order v4 within the NRQCD formalism. We have observed that the NRQCD predictions with their matrix elements computed at finite radial separation yield results which are found to be in better agreement with experimentM values for both di-gamma and di-leptonic decays. The same scenario is seen in the case when di-gamma and di-leptonic decay widths are computed with the Van Royen- Weisskopf formula. It is also observed that the di-gluon decay width with the inclusion of binding energy effects are in better agreement with the experimental data available for 1s-2s and 1P. The di-gluon decay width of 3s and 2P waves waves are Mso predicted. Thus, the present study of decay rates clearly indicates the importance of binding energy effects.

关键词： potential models heavy quarkonia radiative decays non relativistic quark model

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Bilateral sequential femoral neck stress fractures in young adult with HIV infection on antiretroviral therapy: A case report

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World Journal of Orthopedics 2019年第6期10卷 247-254页

作者： saisunder shashank Chaganty Deeptiman James Faculty of Medicine and Dentistry University of PlymouthPlymouth PL6 8BUUnited Kingdom Assistant Professor Department of OrthopedicsChristian Medical CollegeVelloreVellore 632004Tamil NaduIndia

BACKGROUND Femoral neck stress fractures are rarely encountered among young adults and are often associated with either repetitive excessive loading or underlying bone *** research has indicated human immunodeficiency virus(HIV)/antiretroviral therapy(ART)as predisposing agents to osteopenia and osteoporosis related *** report a case of HIV/ART induced insufficiency fracture in a resource limited setting in Central *** aim is to increase awareness and promote screening of HIV/ART related osteopenia and osteoporosis in order to prevent catastrophic orthopaedic *** sUMMARY A 35-year-old HIV positive male presented with a stress fracture of left femoral *** patient was on ART and reported no *** went on to be successfully managed ***,during work-up osteopenia of the contralateral proximal femur was recognised using singh’s *** months post-op the patient presented with right-sided femoral-neck stress *** this stage the patient was nonconcordant with ART and denied surgical *** In the absence of co-morbidities,several mechanisms of HIV/antiretroviral therapy may have played a role in predisposing our patient towards such a *** recommend routine screening all HIV-infected patients for osteopenia,especially in younger *** low resource settings and district hospitals,pelvis radiograph&singh’s index can be used for screening.

关键词： Bilateral femoral neck stress fracture Human immunodeficiency virusantiretroviral therapy related osteopenia Osteoporosis in resource limited setting Human immunodeficiency virus related fragility fractures

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